Page 8 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
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JOURNAL OF HEPATOLOGY
Table 4A. Drug-drug interactions between HCV DAAs and HIV antiretrovirals. Table 4B. Drug-drug interactions between HCV DAAs and illicit recreational
drugs.
SIM DCV SOF SOF/ 3D SOF/
LDV LDV
• SIM DCV SOF 3D
•
Abacavir ••• • • •
Didanosine • •
Emtricitabine ••• • • Amphetamine ••• • •
Lamivudine • Cannabis •
NRTIs Stavudine ••• • • Cocaine ••• • •
Tenofovir • Diamorphine
Zidovudine ••• • • Diazepam ••• • •
Efavirenz • Gamma-hy-
Etravirine ••• • • droxybutyrate ••• • •
Nevirapine Ketamine •
Rilpivirine ••• • • MDMA (ecstasy) ••• • •
Methamphetamine •
Atazanavir; ataza- ••• • • Phencyclidine (PCP) ••• • •
navir/ritonavir Temazepam
Protease inhibitors NNRTIs • • • •* ••• •
Darunavir/ritonavir;
darunavir/cobicistat ••• • ••• •
••• • ••• •
• • • •* ••• •
• • • •* ••• •
• • • •* SIM, simeprevir; DCV, daclatasvir; SOF, sofosbuvir; SOF/LDV, sofosbuvir plus
ledipasvir; 3D, ritonavir-boosted paritaprevir, plus ombitasvir and dasabuvir.
Fosamprenavir • • • •* • Colour legend. Green: No clinically significant interaction expected. Amber:
Potential interaction which may require a dosage adjustment, altered timing of
Lopinavir • • • •* • administration or additional monitoring.
Some drugs may require dose modifications dependent on hepatic function.
Entry/ Saquinavir • • • •* • Please refer to the product label for individual drugs for dosing advice.
Integrase ••• •• The symbol (green, amber) used to rank the clinical significance of the drug
inhibitors Dolutegravir interaction is based on www.hep-druginteractions.org (University of Liverpool).
Elvitegravir/cobi- • • • •* • For additional drug-drug interactions and for a more extensive range of drugs,
cistat detailed pharmacokinetic interaction data and dosage adjustments, refer to the
Maraviroc ••• •• above-mentioned website.
Raltegravir ••• ••
SIM, simeprevir; DCV, daclatasvir; SOF, sofosbuvir; SOF/LDV, sofosbuvir plus Table 4C. Drug-drug interactions between HCV DAAs and lipid lowering drugs.
ledipasvir; 3D, ritonavir-boosted paritaprevir, plus ombitasvir and dasabuvir.
⁄Known or anticipated increase in tenofovir concentrations with boosted regi- SIM DCV SOF SOF/ 3D
mens and with efavirenz and rilpivirine when given sofosbuvir plus ledipasvir: LDV
caution and frequent renal monitoring needed.
Colour legend. Green: No clinically significant interaction expected. Amber: Atorvastatin •••••
Potential interaction which may require a dosage adjustment, altered timing of Bezafibrate
administration or additional monitoring. Red: These drugs should not be co- Ezetimibe •••••
administered. Fenofibrate
Some drugs may require dose modifications dependent on hepatic function. Fluvastatin •••••
Please refer to the product label for individual drugs for dosing advice. Gemfibrozil
The symbol (green, amber, red) used to rank the clinical significance of the Lovastatin •••••
drug interaction is based on www.hep-druginteractions.org (University of Pitavastatin
Liverpool). For additional drug-drug interactions and for a more extensive range Pravastatin •••••
of drugs, detailed pharmacokinetic interaction data and dosage adjustments, refer Rosuvastatin
to the above-mentioned website. Simvastatin •••••
•••••
•••••
ledipasvir is contra-indicated due to a serious risk of symp- •••••
tomatic bradycardia (one lethal case reported). The mechanism
of interaction as well as the role of other co-medications is •••••
unknown and requires investigation. Bradycardia has been
observed within hours to days of starting the DAAs, but cases •••••
have been observed up to 2 weeks after initiating HCV treatment.
SIM, simeprevir; DCV, daclatasvir; SOF, sofosbuvir; SOF/LDV, sofosbuvir plus
Sofosbuvir and ledipasvir are available in a two-drug fixed- ledipasvir; 3D, ritonavir-boosted paritaprevir, plus ombitasvir and dasabuvir.
dose combination containing 400 mg of sofosbuvir and 90 mg of Colour legend. Green: No clinically significant interaction expected. Amber:
ledipasvir in a single tablet. The recommended dose of the com- Potential interaction which may require a dosage adjustment, altered timing of
bination is one tablet taken orally once daily with or without food. administration or additional monitoring. Red: These drugs should not be co-
administered.
Biliary excretion of unchanged ledipasvir is the major route of Some drugs may require dose modifications dependent on hepatic function.
elimination with renal excretion being a minor pathway Please refer to the product label for individual drugs for dosing advice.
(approximately 1%), whereas sofosbuvir is principally renally The symbol (green, amber, red) used to rank the clinical significance of the
excreted, as noted above. The median terminal half-lives of sofos- drug interaction is based on www.hep-druginteractions.org (University of
buvir and its predominant metabolite GS-331007 following Liverpool). For additional drug-drug interactions and for a more extensive range
administration of sofosbuvir/ledipasvir were 0.5 and 27 h, of drugs, detailed pharmacokinetic interaction data and dosage adjustments, refer
respectively. Neither sofosbuvir nor ledipasvir are substrates for to the above-mentioned website.
hepatic uptake transporters; GS-331007 is not a substrate for
renal transporters. Ledipasvir plasma exposure (AUC) was similar in patients
with severe hepatic impairment and control patients with normal
hepatic function. Population pharmacokinetics analysis in HCV-
infected patients indicated that cirrhosis (including
7
Table 4A. Drug-drug interactions between HCV DAAs and HIV antiretrovirals. Table 4B. Drug-drug interactions between HCV DAAs and illicit recreational
drugs.
SIM DCV SOF SOF/ 3D SOF/
LDV LDV
• SIM DCV SOF 3D
•
Abacavir ••• • • •
Didanosine • •
Emtricitabine ••• • • Amphetamine ••• • •
Lamivudine • Cannabis •
NRTIs Stavudine ••• • • Cocaine ••• • •
Tenofovir • Diamorphine
Zidovudine ••• • • Diazepam ••• • •
Efavirenz • Gamma-hy-
Etravirine ••• • • droxybutyrate ••• • •
Nevirapine Ketamine •
Rilpivirine ••• • • MDMA (ecstasy) ••• • •
Methamphetamine •
Atazanavir; ataza- ••• • • Phencyclidine (PCP) ••• • •
navir/ritonavir Temazepam
Protease inhibitors NNRTIs • • • •* ••• •
Darunavir/ritonavir;
darunavir/cobicistat ••• • ••• •
••• • ••• •
• • • •* ••• •
• • • •* ••• •
• • • •* SIM, simeprevir; DCV, daclatasvir; SOF, sofosbuvir; SOF/LDV, sofosbuvir plus
ledipasvir; 3D, ritonavir-boosted paritaprevir, plus ombitasvir and dasabuvir.
Fosamprenavir • • • •* • Colour legend. Green: No clinically significant interaction expected. Amber:
Potential interaction which may require a dosage adjustment, altered timing of
Lopinavir • • • •* • administration or additional monitoring.
Some drugs may require dose modifications dependent on hepatic function.
Entry/ Saquinavir • • • •* • Please refer to the product label for individual drugs for dosing advice.
Integrase ••• •• The symbol (green, amber) used to rank the clinical significance of the drug
inhibitors Dolutegravir interaction is based on www.hep-druginteractions.org (University of Liverpool).
Elvitegravir/cobi- • • • •* • For additional drug-drug interactions and for a more extensive range of drugs,
cistat detailed pharmacokinetic interaction data and dosage adjustments, refer to the
Maraviroc ••• •• above-mentioned website.
Raltegravir ••• ••
SIM, simeprevir; DCV, daclatasvir; SOF, sofosbuvir; SOF/LDV, sofosbuvir plus Table 4C. Drug-drug interactions between HCV DAAs and lipid lowering drugs.
ledipasvir; 3D, ritonavir-boosted paritaprevir, plus ombitasvir and dasabuvir.
⁄Known or anticipated increase in tenofovir concentrations with boosted regi- SIM DCV SOF SOF/ 3D
mens and with efavirenz and rilpivirine when given sofosbuvir plus ledipasvir: LDV
caution and frequent renal monitoring needed.
Colour legend. Green: No clinically significant interaction expected. Amber: Atorvastatin •••••
Potential interaction which may require a dosage adjustment, altered timing of Bezafibrate
administration or additional monitoring. Red: These drugs should not be co- Ezetimibe •••••
administered. Fenofibrate
Some drugs may require dose modifications dependent on hepatic function. Fluvastatin •••••
Please refer to the product label for individual drugs for dosing advice. Gemfibrozil
The symbol (green, amber, red) used to rank the clinical significance of the Lovastatin •••••
drug interaction is based on www.hep-druginteractions.org (University of Pitavastatin
Liverpool). For additional drug-drug interactions and for a more extensive range Pravastatin •••••
of drugs, detailed pharmacokinetic interaction data and dosage adjustments, refer Rosuvastatin
to the above-mentioned website. Simvastatin •••••
•••••
•••••
ledipasvir is contra-indicated due to a serious risk of symp- •••••
tomatic bradycardia (one lethal case reported). The mechanism
of interaction as well as the role of other co-medications is •••••
unknown and requires investigation. Bradycardia has been
observed within hours to days of starting the DAAs, but cases •••••
have been observed up to 2 weeks after initiating HCV treatment.
SIM, simeprevir; DCV, daclatasvir; SOF, sofosbuvir; SOF/LDV, sofosbuvir plus
Sofosbuvir and ledipasvir are available in a two-drug fixed- ledipasvir; 3D, ritonavir-boosted paritaprevir, plus ombitasvir and dasabuvir.
dose combination containing 400 mg of sofosbuvir and 90 mg of Colour legend. Green: No clinically significant interaction expected. Amber:
ledipasvir in a single tablet. The recommended dose of the com- Potential interaction which may require a dosage adjustment, altered timing of
bination is one tablet taken orally once daily with or without food. administration or additional monitoring. Red: These drugs should not be co-
administered.
Biliary excretion of unchanged ledipasvir is the major route of Some drugs may require dose modifications dependent on hepatic function.
elimination with renal excretion being a minor pathway Please refer to the product label for individual drugs for dosing advice.
(approximately 1%), whereas sofosbuvir is principally renally The symbol (green, amber, red) used to rank the clinical significance of the
excreted, as noted above. The median terminal half-lives of sofos- drug interaction is based on www.hep-druginteractions.org (University of
buvir and its predominant metabolite GS-331007 following Liverpool). For additional drug-drug interactions and for a more extensive range
administration of sofosbuvir/ledipasvir were 0.5 and 27 h, of drugs, detailed pharmacokinetic interaction data and dosage adjustments, refer
respectively. Neither sofosbuvir nor ledipasvir are substrates for to the above-mentioned website.
hepatic uptake transporters; GS-331007 is not a substrate for
renal transporters. Ledipasvir plasma exposure (AUC) was similar in patients
with severe hepatic impairment and control patients with normal
hepatic function. Population pharmacokinetics analysis in HCV-
infected patients indicated that cirrhosis (including
7
